Efficacy and safety of low‐dose otelixizumab anti‐CD 3 monoclonal antibody in preserving C‐peptide secretion in adolescent type 1 diabetes: DEFEND‐2, a …

P Ambery, TW Donner, N Biswas… - Diabetic …, 2014 - Wiley Online Library
P Ambery, TW Donner, N Biswas, J Donaldson, J Parkin, CM Dayan
Diabetic medicine, 2014Wiley Online Library
Abstract Aims Phase III DEFEND‐2 investigated whether otelixizumab (3.1 mg over 8 days)
preserved C‐peptide secretion in patients with new‐onset Type 1 diabetes, focusing on
adolescents (12–17 years). Methods One hundred and seventy‐nine patients (54
adolescents) were randomized to otelixizumab or placebo. The primary endpoint was
change in 2‐h mixed‐meal‐stimulated C‐peptide area under the curve at month 12.
Enrolment was suspended in April 2011 following negative efficacy results from DEFEND‐1 …
Aims
Phase III DEFEND‐2 investigated whether otelixizumab (3.1 mg over 8 days) preserved C‐peptide secretion in patients with new‐onset Type 1 diabetes, focusing on adolescents (12–17 years).
Methods
One hundred and seventy‐nine patients (54 adolescents) were randomized to otelixizumab or placebo. The primary endpoint was change in 2‐h mixed‐meal‐stimulated C‐peptide area under the curve at month 12. Enrolment was suspended in April 2011 following negative efficacy results from DEFEND‐1. DEFEND‐2 terminated early after 12 months' efficacy and safety follow‐up.
Results
Change from baseline C‐peptide was not significantly different [∆ = –0.09 nmol/l (95% CI –0.17 to 0; = 0.051)]. No differential C‐peptide effect was seen for otelixizumab in adolescents and more adverse events were reported.
Conclusions
Efficacy and tolerability of otelixizumab was similar to DEFEND‐1. The 3.1‐mg dose was non‐efficacious in adults and adolescents. Further investigation of the mechanism of action seen at higher doses and therapeutic window is required.
Clinical Trials Registry No: NCT 00763451
Wiley Online Library